Chronic activation of immune mechanisms contribute to the pathophysiology of hypertension and renal dysfunction. Women with hypertension, especially during pregnancy, have elevated circulating cytokines, neutrophils and lymphocytes producing an agonistic autoantibody to the angiotensin II type I receptor (AT1-AA). However, the exact pathway linking placental ischemia and immune activation with the development of hypertension during pregnancy has yet to be clearly defined. One possible mechanism is that chronic inflammation resulting in the AT1-AA promotes oxidative stress and endothelial dysfunction leading to altered renal hemodynamics and reduced renal pressure natriuresis by enhanced interactions with Angiotensin II and the Angiotensin II type 1 receptor. We have shown that reduced uterine perfusion pressure (RUPP) in pregnant rats, a rat model of preeclampsia, is an important stimulus for the production of the AT1-AA. While recent studies have suggested a role for CD4+T lymphocytes and a dysregulation among T regulatory (?TReg)and T helper 17 cells (?THelper 17) in the chronic immune activation seen in PE, the importance of the alteration of these subsets of T cells in the production of the AT1-AA and hypertension during pregnancy remains unclear. Although, my mentor has shown that purified AT1-AA activates various signaling pathways such as endothelin -1 (ET-1) and reactive oxygen species (ROS), via the AT1 receptor to cause hypertension in pregnant rodents, we don't know the importance of altered T regs/ Thelper 17 in influencing these AT1-AA stimulated mechanisms during PE. Therefore the focus of my proposal will investigate a role for increased Thelper 17 in response to placental ischemia to cause hypertension by stimulating AT1-AA mediated ET-1 or oxidative stress during pregnancy. In addition, we will examine the effect of supplementation of NP T regs and IL-10 to suppress hypertension and AT1-AA in a rat model of PE. Based on these novel preliminary findings, the central hypothesis to be tested in this proposal is that hypertension in response to placental ischemia in pregnant rats associated with ?T regs and ?Thelper 17 which in turn facilitate the production of AT1-AA via B lymphocytes. In addition, we propose that the supplementation of normal pregnant T reg cells or their cytokine (IL-10) will prevent the production of AT1-AA and hypertension in the RUPP rat model of PE. Furthermore we will examine the effect of these CD4 T cell subsets to enhance the production of ET-1 and ROS leading to decreased renal hemodynamics and hypertension during pregnancy. To test this hypothesis an integrative physiological approach complemented with molecular, immunological, in vitro cell culture and in vivo techniques will be used to address the following 2 specific aims: Aim 1: To test the hypothesis that ?CD4+T regulatory cells or IL-10 promote AT1-AA, ET-1 or ROS mediated hypertension in response to placental ischemia during pregnancy. Aim 2: To test the hypothesis that placental ischemia induced ?TH17 leads to AT1- AA, ET-1 and ROS mediated increased blood pressure and decreased renal hemodynamics in pregnant rats